Electrochemical Cyclization of o-Aminyl Azobenzenes: Roles of Aldehydes in N-N Bond Cleavage.

Direct functionalization of azobenzenes provides an approach to obtaining valuable molecules in synthetic chemistry. However, an efficient method for the cleavage of the N═N bond of azobenzenes, which is a key process for this transformation, is still lacking. We herein disclose an electrochemical reduction-induced cyclization of azobenzenes with aldehydes via N═N bond cleavage. This electrochemical cyclization of azobenzenes proceeds well in the absence of any transition metals or external chemical oxidants, leading to the formation of N-protected benzimidazoles in moderate to good yields.

Improvement of nucleotide content of Cordyceps tenuipes by Schisandra chinensis: fermentation process optimization and application prospects.

Nucleotides are important components and the main indicators for judging Cordyceps quality. In this paper, the mixed fermentation process of Schisandra chinensis and Cordyceps tenuipes was systematically studied, and it was proposed that the fermentation products aqueous extract (S-ZAE) had antioxidant activity and anti-AChE ability. Herein, the results of a single factor showed that S. chinensis, yeast extract, inoculum amount, and pH had significant effects on nucleotide synthesis. The fermentation process optimization results were 3% glucose, 0.25% KH2PO4, 2.1% yeast extract, and S. chinensis 0.49% (m/v), the optimal fermentation conditions were 25℃, inoculum 5.8% (v/v), pH 3.8, 6 d. The yield of total nucleotides in the scale-up culture was 0.64 ± 0.027 mg/mL, which was 10.6 times higher than before optimization. S-ZAE has good antioxidant and anti-AChE activities (IC50 0.50 ± 0.050 mg/mL). This fermentation method has the advantage of industrialization, and its fermentation products have the potential to become good functional foods or natural therapeutic agents.

Higher ambient temperatures may worsen obstructive sleep apnea: A nationwide smartwatch-based analysis of 6.2 million person-days.

Obstructive sleep apnea (OSA) is a serious type of sleep disorder that can lead to cardiometabolic and neurocognitive diseases. We utilized smart device-based photoplethysmography technology to collect sleep data from the Chinese population from 2019 to 2022. Distributed lag nonlinear models combined with a generalized nonlinear model or a linear mixed effects model were used to investigate the short-term associations between daily temperature and indicators of OSA severity. We included a total of 6,232,056 d of sleep monitoring data from 51,842 participants with moderate to severe risk of OSA from 313 Chinese cities. The relationships between ambient temperature and OSA exacerbation, apnea-hypopnea index (AHI), and minimum oxygen saturation (MinSpO2) were almost linear and present only on the same day. Higher temperatures were associated with a greater risk of OSA exacerbation, with an 8.4% (95% confidence interval (CI): 7.6%-9.3%) increase per 10 °C increase in temperature. A 10 °C increase in daily temperature corresponded to an AHI increase of 0.70 events/h (95% CI: 0.65-0.76) and a MinSpO2 decrease of 0.18% (95% CI: 0.16%-0.19%). Exposure to elevated temperatures during the night can also lead to adverse effects. The effects of higher temperatures on OSA severity were stronger among men, participants with a body mass index ≥ 24 kg/m2, those aged 45 years and older, individuals with a history of hypertension and diabetes, and during the cold season. This large-scale, nationwide, longitudinal study provides robust evidence suggesting that higher ambient temperatures may immediately worsen OSA.

Air pollutants, genetic susceptibility, and incident schizophrenia in later life: A prospective study in the UK Biobank.

OBJECTIVE: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late-onset schizophrenia and evaluate whether genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. RESULTS: An interquartile range increase in PM2.5, PM10, NO2, and NOx was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure-response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM10, NO2, and NOx with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. CONCLUSION: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late-onset schizophrenia in an aging era, especially among those with high genetic risks.

Ultrasound elastography predicts anticoagulation in lower extremity deep vein thrombosis.

OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

Dimeric eremophilane-type sesquiterpenoids from the peeled stems of Syringa pinnatifolia.

A continued phytochemical investigation guided by 1H NMR and LC-MS data on the ethanol extract from the peeled stems of Syringa pinnatifolia Hemsl. led to the isolation of 16 undescribed dimeric eremophilane sesquiterpenoids, namely syringenes R-Z (1-9) and A1-G1 (10-16). These structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, NMR, quantum-mechanics-based computational analysis of NMR chemical shifts, and single-crystal X-ray diffraction analyses, and a concise rule for determination of relative configuration of angular methyl was proposed. The results of the cardioprotective assay demonstrated that 3 exhibits a protective effect against hypoxia-induced injuries in H9c2 cells. This effect was observed at a concentration of 10 µM, with a protective rate of 28.43 ± 11.80%.

Long-term exposure to ambient air pollution and incident gout: A prospective cohort study in the UK Biobank.

Gout is a chronic disorder characterized by the accumulation of uric acid in the body, leading to recurrent episodes of joint inflammation and pain. There remains a lack of studies investigating the association between long-term exposure to ambient air pollution and the incidence of gout. We conducted this prospective cohort study involving participants aged 38-70 from the UK Biobank who were enrolled in 2006-2010 and followed until 2023. Baseline residential concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were predicted using land-use regression models. Cox proportional hazards models were employed to examine the relationship between air pollution and incident gout events. A total of 443,587 individuals were included in the analyses and a total of 6589 incident gout cases were identified over a follow-up of 6,130,439 person-years. There were significant associations between higher levels of air pollution and an increased incidence risk of gout. Higher risk of incident gout was associated with each interquartile range increase in concentrations of PM2.5 (hazard ratio:1.05, 95% confidence intervals: 1.02-1.09), PM10 (1.04, 1.00-1.07), NO2 (1.08, 1.05-1.12) and NOx (1.04, 1.02-1.07). The magnitude of associations was larger at higher concentrations. The association was more prominent among older adults, smokers, and individuals with lower and moderate physical activity. This prospective cohort study provides novel and compelling evidence of increased risk of incident gout associated with long-term air pollution exposures.

Unlocking a Sustainable Future for Plastics: A Chemical-Enzymatic Pathway for Efficient Conversion of Mixed Waste to MHET and Energy-Saving PET Recycling.

The heterogeneous monomers obtained from plastic waste degradation are unfavorable for PET recondensation and high-value derivative synthesis. Herein, we developed an efficient chemical-enzymatic approach to convert mixed plastic wastes into homogeneous mono-2-hydroxyethyl terephthalate (MHET) without downstream purification, benefiting from three discovered BHETases (KbEst, KbHyd, and BrevEst) in nature. Towards the mixed plastic waste, integrating the chemical K2CO3-driven glycolysis process with the BHETase depolymerization technique resulted in an MHET yield of up to 98.26 % in 40 h. Remarkably, BrevEst accomplished the highest BHET hydrolysis (~87 % efficiency in 12 h) for yielding analytical-grade MHET compared to seven state-of-the-art PET hydrolases (18 %-40 %). In an investigation combining quantum theoretical computations and experimental validations, we established a MHET-initiated PET repolymerization pathway. This shortcut approach with MHET promises to strengthen the valorization of mixed plastics, offering a substantially more efficient and energy-saving route for PET recycling.

Empowering Protein Engineering through Recombination of Beneficial Substitutions.

Directed evolution stands as a seminal technology for generating novel protein functionalities, a cornerstone in biocatalysis, metabolic engineering, and synthetic biology. Today, with the development of various mutagenesis methods and advanced analytical machines, the challenge of diversity generation and high-throughput screening platforms is largely solved, and one of the remaining challenges is: how to empower the potential of single beneficial substitutions with recombination to achieve the epistatic effect. This review overviews experimental and computer-assisted recombination methods in protein engineering campaigns. In addition, integrated and machine learning-guided strategies were highlighted to discuss how these recombination approaches contribute to generating the screening library with better diversity, coverage, and size. A decision tree was finally summarized to guide the further selection of proper recombination strategies in practice, which was beneficial for accelerating protein engineering.

Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

Spatiotemporal observations of host-pathogen interactions in mucosa during SARS-CoV-2 infection indicate a protective role of ILC2s.

IMPORTANCE: Our study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019.

Air pollution may increase the sleep apnea severity: A nationwide analysis of smart device-based monitoring.

Obstructive sleep apnea (OSA) can lead to sleep deprivation, accidents, and cardiovascular diseases. However, research on the short-term effects of air pollutants on OSA severity is limited and inconsistent. We conducted a novel case time series analysis using a nationwide dataset among Huawei smart device users to assess the association between air pollution and OSA severity in a population at moderate-to-severe risk of OSA. Fixed-effects regression models were used to assess the associations between air pollution and the risk of OSA exacerbation, apnea-hypopnea index (AHI), and oxygen saturation. A total of 51,842 participants who were at moderate-to-severe risk of OSA (mean age [SD]: 45.4 [11.0], 95.5% male) were included, with 6,232,056 person-days of monitoring. The associations of fine particulate matter, nitrogen dioxide, carbon monoxide, and sulfur dioxide with OSA severity could occur during the sleep period, and last for 2 days. An increase of 1 interquartile range in the moving average concentrations of air pollution during the sleep period and the 2 previous days was associated with a 1.14%-4.31% increase in the risk of OSA exacerbation, an increase in AHI by 0.05-0.17 events/h, and a decrease in oxygen saturation (%) by 0.003-0.014. The exposure-response curves were almost linear. The associations between air pollutants and OSA were consistently stronger in participants aged 45 years or older. By virtue of the smart device-based technology, this large-scale, nationwide, longitudinal study provides compelling evidence that short-term exposure to air pollution may worsen sleep apnea. Our findings highlight the significance of ongoing efforts to improve air quality in mitigating OSA severity and the relevant disease burden in an aging era.

Cyclization of Azobenzenes Via Electrochemical Oxidation Induced Benzylic Radical Generation.

An electrochemical oxidation-induced cyclization of ortho-alkyl-substituted azobenzenes has been developed. The direct electrochemical benzylic C-H functionalization with respect to azobenzenes could proceed in the absence of any catalyst or external chemical oxidant to afford a number of 2H-indazole derivatives in moderate to good yields. This protocol enables the reuse of the byproduct to the same 2H-indazoles, thus significantly reducing pollution discharge in synthetic chemistry.

Discovery and mechanism-guided engineering of BHET hydrolases for improved PET recycling and upcycling.

Although considerable research achievements have been made to address the plastic crisis using enzymes, their applications are limited due to incomplete degradation and low efficiency. Herein, we report the identification and subsequent engineering of BHETases, which have the potential to improve the efficiency of PET recycling and upcycling. Two BHETases (ChryBHETase and BsEst) are identified from the environment via enzyme mining. Subsequently, mechanism-guided barrier engineering is employed to yield two robust and thermostable ΔBHETases with up to 3.5-fold enhanced kcat/KM than wild-type, followed by atomic resolution understanding. Coupling ΔBHETase into a two-enzyme system overcomes the challenge of heterogeneous product formation and results in up to 7.0-fold improved TPA production than seven state-of-the-art PET hydrolases, under the conditions used here. Finally, we employ a ΔBHETase-joined tandem chemical-enzymatic approach to valorize 21 commercial post-consumed plastics into virgin PET and an example chemical (p-phthaloyl chloride) for achieving the closed-loop PET recycling and open-loop PET upcycling.

Engineering All-Round Cellulase for Bioethanol Production.

One strategy to decrease both the consumption of crude oil and environmental damage is through the production of bioethanol from biomass. Cellulolytic enzyme stability and enzymatic hydrolysis play important roles in the bioethanol process. However, the gradually increased ethanol concentration often reduces enzyme activity and leads to inactivation, thereby limiting the final ethanol yield. Herein, we employed an optimized Two-Gene Recombination Process (2GenReP) approach to evolve the exemplary cellulase CBHI for practical bioethanol fermentation. Two all-round CBHI variants (named as R2 and R4) were obtained with simultaneously improved ethanol resistance, organic solvent inhibitor tolerance, and enzymolysis stability in simultaneous saccharification and fermentation (SSF). Notably, CBHI R4 had a 7.0- to 34.5-fold enhanced catalytic efficiency (kcat/KM) in the presence/absence of ethanol. Employing the evolved CBHI R2 and R4 in the 1G bioethanol process resulted in up to 10.27% (6.7 g/L) improved ethanol yield (ethanol concentration) than non-cellulase, which was far more beyond than other optimization strategies. Besides bioenergy fields, this transferable protein engineering routine holds the potential to generate all-round enzymes that meet the requirement in biotransformation and bioenergy fields.

A cross-sectional study of non-suicidal self-injury in a Chinese adolescent inpatient cohort.

Background: Non-suicidal self-injury (NSSI) is a significant predictor of completed suicide and is increasingly recognized as a serious public health concern. Multiple factors, including social, familial, mental, and genetic factors could influence the occurrence of this behavior. Identifying the early risk factors is important for screening and preventing this behavior. Methods: Here, we recruited a total of 742 adolescent inpatient participants from a mental health center and conducted a series of diagnostic interviews and questionnaires to assess NSSI behavior and other events. Bivariate analysis was used to detect differences between groups in NSSI and non-NSSI. Then, binary logistic regression was fitted to identify predictors of NSSI as a function of these questionnaire scores. Results: Of the 742 adolescents examined, a total of 382 (51.5%) participants engaged in NSSI. Bivariate analysis showed that age, gender, depression, anxiety, insomnia, and childhood trauma was significantly associated with NSSI. Logistic regression results suggested that females had 2.43 higher odds of engaging in NSSI when compared to their male counterparts (OR = 3.43, 95%CI = 2.09-5.74, p = 1.70 × 10-6). Depression was a primary risk predictor for NSSI with each additional increase in symptoms of depression increasing the odds of engaging in NSSI by 18% (OR = 1.18, 95%CI = 1.12-1.25, p = 2.25 × 10-8). Conclusion: More than half of the adolescent inpatients with psychiatric disorders have NSSI experience. Depression and gender were the risk factors for NSSI. Age at a specific range had a high prevalence of NSSI.

Global plastic upcycling during and after the COVID-19 pandemic: The status and perspective.

Plastic pollution has become one of the most pressing environmental issues worldwide since the vast majority of post-consumer plastics are hard to degrade in the environment. The coronavirus disease (COVID-19) pandemic had disrupted the previous effort of plastic pollution mitigation to a great extent due to the overflow of plastic-based medical waste. In the post-pandemic era, the remaining challenge is how to motivate global action towards a plastic circular economy. The need for one package of sustainable and systematic plastic upcycling approaches has never been greater to address such a challenge. In this review, we summarized the threat of plastic pollution during COVID-19 to public health and ecosystem. In order to solve the aforementioned challenges, we present a shifting concept, regeneration value from plastic waste, that provides four promising pathways to achieve a sustainable circular economy: 1) Increasing reusability and biodegradability of plastics; 2) Transforming plastic waste into high-value products by chemical approaches; 3) The closed-loop recycling can be promoted by biodegradation; 4) Involving renewable energy into plastic upcycling. Additionally, the joint efforts from different social perspectives are also encouraged to create the necessary economic and environmental impetus for a circular economy.

[Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia].

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

Evolving Robust and Interpretable Enzymes for the Bioethanol Industry.

Obtaining a robust and applicable enzyme for bioethanol production is a dream for biorefinery engineers. Herein, we describe a general method to evolve an all-round and interpretable enzyme that can be directly employed in the bioethanol industry. By integrating the transferable protein evolution strategy InSiReP 2.0 (In Silico guided Recombination Process), enzymatic characterization for actual production, and computational molecular understanding, the model cellulase PvCel5A (endoglucanase II Cel5A from Penicillium verruculosum) was successfully evolved to overcome the remaining challenges of low ethanol and temperature tolerance, which primarily limited biomass transformation and bioethanol yield. Remarkably, application of the PvCel5A variants in both first- and second-generation bioethanol production processes (i. Conventional corn ethanol fermentation combined with the in situ pretreatment process; ii. cellulosic ethanol fermentation process) resulted in a 5.7-10.1 % increase in the ethanol yield, which was unlikely to be achieved by other optimization techniques.

Syringenes M - Q, Eremophilane Sesquiterpenoid Dimers from the Peeled Stems of Syringa pinnatifolia.

As a part of systematic studies on Syringa pinnatifolia, a continued phytochemical investigation guided by 1 H-NMR and LC/MS data on the ethanol extract afforded five new dimeric eremophilane sesquiterpenoids, namely syringenes M-Q (1-5). These structures were elucidated by extensive analysis of spectroscopic data, including infrared (IR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR), quantum-mechanics-based computational analysis of NMR chemical shifts, and single-crystal X-ray diffraction. Compounds 4 and 5 showed inhibitory activities against NO production induced by lipopolysaccharide in RAW264.7 macrophage cells, with IC50 values of 5.1 and 9.3 µM, compared to positive control indomethacin (IC50 33.6 µM). These dimeric eremophilane sesquiterpenoids may be potential markers for discriminating this species from the genus Syringa and the Oleaceae family.